Skip to main content

Advertisement

Response to ‘T-helper 17 cell cytokines and interferon type I: partners in crime in systemic lupus erythematosus?’ – Authors’ reply

We would like to reply to the letter by Dolff and colleagues [1] regarding our article in a recent issue of Arthritis Research & Therapy [2]. We thank the authors for their interest in our work and the critical reading of our article. The aim of our study was to investigate a possible association between the IFN type I signature and memory T helper 17 (Th17) cells and their cytokines in systemic lupus erythematosus (SLE). Since CCR6 can be expressed by regulatory T (Treg) cells, we have excluded CD25high cells to discriminate between CD4+CD45RO+CCR6+CD25 (primary Th17 cells) and Treg cells. Concerning the observation on co-expression of IL-17A with IFN-γ, we would like to remark that IFN-γ is an IFN type II, and not an IFN type I, cytokine and does not bind to the IFN type I receptor. Detection of IFN type I activity is hampered by the difficulty to assess the different subtypes of this cytokine. Therefore, analysis of IFN type I-induced gene expression in RNA from peripheral blood cells, the so-called IFN type I signature, is used as a measure for IFN type I activity. Although we fully agree with the authors that the relationship between Th cells and IFN type I deserves further study, their remark on the ‘genetic’ signature is confusing and probably refers to the IFN type I-induced gene expression signature, which is detected at the RNA level.

The relationship between CD25+ Tregs and IFN type I is certainly of interest for further study as these Tregs are carrying the IFN type I receptor and thus respond to increased systemic IFN type I activity in SLE. Also, follow-up studies with a focus on adaptive and innate cells producing IL-17, including the relation with IL-21 and IL-22 and plasticity, will be of interest [3, 4]. In our article, we presented data supporting a potential co-activity between IFN type I and CD4+memory CCR6+ Th17 cytokines. Further studies are needed to confirm this co-activity with a focus on revealing the mechanism of this dangerous link in SLE.

Abbreviations

IFN:

Interferon

IL:

Interleukin

SLE:

Systemic lupus erythematosus

Th17:

T helper 17

Treg:

Regulatory T.

References

  1. 1.

    Dolff S, Abdulahad WH, Kallenberg CGM: Response to ‘T-helper 17 cell cytokines and interferon type I: partners in crime in systemic lupus erythematosus?’. Arthritis Res Ther. 2014, 16: 409-10.1186/ar4576.

  2. 2.

    Brkic Z, Corneth OB, van Helden-Meeuwsen CG, Dolhain RJ, Maria NI, Paulissen SM, Davelaar N, van Hamburg JP, van Daele PL, Dalm VA, van Hagen PM, Hazes JM, Versnel MA, Lubberts E: T helper 17 cell cytokines and interferon type I: partners in crime in systemic lupus erythematosus?. Arthritis Res Ther. 2014, 16: R62-10.1186/ar4499.

  3. 3.

    Acosta-Rodriguez EV, Rivino L, Geginat J, Jarrossay D, Gattorno M, Lanzavecchia A, Sallusto F, Napolitani G: Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells. Nat Immunol. 2007, 8: 639-646. 10.1038/ni1467.

  4. 4.

    Hirota K, Duarte JH, Veldhoen M, Hornsby E, Li Y, Cua DJ, Ahlfors H, Wilhelm C, Tolaini M, Menzel U, Garefalaki A, Potocnik AJ, Stockinger B: Fate mapping of IL-17-producing T cells in inflammatory responses. Nat Immunol. 2011, 12: 255-263. 10.1038/ni.1993.

Download references

Author information

Correspondence to Erik Lubberts.

Additional information

Competing interests

The authors declare that they have no competing interests.

Marjan A Versnel and Erik Lubberts contributed equally to this work.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Keywords

  • Systemic Lupus Erythematosus
  • Interferon
  • Th17 Cell
  • Treg Cell
  • Expression Signature